tbuckley/cabot-search huggingface dataset:
Multiomics and spatial mapping characterizes human CD8 <sup>+</sup> T cell states in cancer
Authors: Stefan Naulaerts, Angeliki Datsi, Daniel M. Borras, Asier Antoranz Martinez, Julie Messiaen, Isaure Vanmeerbeek, Jenny Sprooten, Raquel S. Laureano, Jannes Govaerts, Dena Panovska, Marleen Derweduwe, Michael C. Sabel, Marion Rapp, Weiming Ni, Sean Mackay, Yannick Van Herck, Lendert Gelens, Tom Venken, Sanket More, Oliver Bechter, Gabriele Bergers, Adrian Liston, Steven De Vleeschouwer, Benoit J. Van Den Eynde, Diether Lambrechts, Michiel Verfaillie, Francesca Bosisio, Sabine Tejpar, Jannie Borst, Rüdiger V. Sorg, Frederik De Smet, Abhishek D. Garg
Journal: Science Translational Medicine (2023)

Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8 + T cells remain disputed. Using multiomics analysis of CD8 + T cell features across multiple patient cohorts and tumor types, we identified tumor niche–dependent exhausted and other types of hypofunctional CD8 + T cell states. CD8 + T cells in “supportive” niches, like melanoma or lung cancer, exhibited features of tumor reactivity–driven exhaustion (CD8 + T EX ). These included a proficient effector memory phenotype, an expanded T cell receptor (TCR) repertoire linked to effector exhaustion signaling, and a cancer-relevant T cell–activating immunopeptidome composed of largely shared cancer antigens or neoantigens. In contrast, “nonsupportive” niches, like glioblastoma, were enriched for features of hypofunctionality distinct from canonical exhaustion. This included immature or insufficiently activated T cell states, high wound healing signatures, nonexpanded TCR repertoires linked to anti-inflammatory signaling, high T cell–recognizable self-epitopes, and an antiproliferative state linked to stress or prodeath responses. In situ spatial mapping of glioblastoma highlighted the prevalence of dysfunctional CD4 + :CD8 + T cell interactions, whereas ex vivo single-cell secretome mapping of glioblastoma CD8 + T cells confirmed negligible effector functionality and a promyeloid, wound healing–like chemokine profile. Within immuno-oncology clinical trials, anti–programmed cell death protein 1 (PD-1) immunotherapy facilitated glioblastoma’s tolerogenic disparities, whereas dendritic cell (DC) vaccines partly corrected them. Accordingly, recipients of a DC vaccine for glioblastoma had high effector memory CD8 + T cells and evidence of antigen-specific immunity. Collectively, we provide an atlas for assessing different CD8 + T cell hypofunctional states in immunogenic versus nonimmunogenic cancers.
Deep Learning on Bone Scintigraphy to Detect Abnormal Cardiac Uptake at Risk of Cardiac Amyloidosis
Authors: Marc-Antoine Delbarre, François Girardon, Lucien Roquette, Paul Blanc-Durand, Marc-Antoine Hubaut, Éric Hachulla, Franck Semah, Damien Huglo, Nicolas Garcelon, Etienne Marchal, Isabelle El Esper, Christophe Tribouilloy, Nicolas Lamblin, Pierre Duhaut, Jean Schmidt, Emmanuel Itti, Thibaud Damy
Journal: JACC. Cardiovascular imaging (2023)

Cardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients. The authors sought to develop and validate a deep learning–based model that automatically detects significant cardiac uptake (Perugini grade ≥2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis. The model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set. The training data set consisted of 3,048 images: 281 positives (Perugini grade ≥2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age <90 years, body mass index, injection-acquisition delay, radionuclides, and the indication of WBS only slightly affected performances. The authors' detection model is effective at identifying patients with cardiac uptake Perugini grade ≥2 on WBS and may help in the diagnosis of patients with cardiac amyloidosis.
Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging
Authors: Elisa Rauseo, Ahmed Salih, Zahra Raisi-Estabragh, Nay Aung, Neha Khanderia, Gregory G. Slabaugh, Charles R. Marshall, Stefan Neubauer, Petia Radeva, Ilaria Boscolo Galazzo, Gloria Menegaz, Steffen E. Petersen
Journal: JACC. Cardiovascular imaging (2023)

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging–derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles. The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function. Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237). Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia. Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.
Vascular Amyloid Deposition Is Highly Prevalent in Immunoglobulin Light Chain Cardiac Amyloidosis
Authors: Jung Woo Kwon, Aliya N. Husain, Jeffrey Mueller, Varun Subashchandran, Nazia Alvi, Karolina M. Zareba, Nitasha Sarswat, Karima Addetia, Amit R. Patel, Jeremy A. Slivnick
Journal: JACC. Cardiovascular imaging (2023)
A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy
Authors: Tony S. Eteläinen, M. Catarina Silva, Johanna K. Uhari-Väänänen, Francesca De Lorenzo, Maria H. Jäntti, Hengjing Cui, Marta Chavero-Pieres, Tommi Kilpeläinen, Christina Mechtler, Reinis Svarcbahs, Erin Seppälä, Juha R. Savinainen, Elena Puris, Gert Fricker, Mikko Gynther, Ulrika H. Julku, Henri J. Huttunen, Stephen J. Haggarty, Timo T. Myöhänen
Journal: Science Translational Medicine (2023)

Tauopathies are neurodegenerative diseases that are characterized by accumulation of hyperphosphorylated tau protein, higher-order aggregates, and tau filaments. Protein phosphatase 2A (PP2A) is a major tau dephosphorylating phosphatase, and a decrease in its activity has been demonstrated in tauopathies, including Alzheimer's disease. Prolyl oligopeptidase is a serine protease that is associated with neurodegeneration, and its inhibition normalizes PP2A activity without toxicity under pathological conditions. Here, we assessed whether prolyl oligopeptidase inhibition could protect against tau-mediated toxicity in cellular models in vitro and in the PS19 transgenic mouse model of tauopathy carrying the human tau-P301S mutation. We show that inhibition of prolyl oligopeptidase with the inhibitor KYP-2047 reduced tau aggregation in tau-transfected HEK-293 cells and N2A cells as well as in human iPSC-derived neurons carrying either the P301L or tau-A152T mutation. Treatment with KYP-2047 resulted in increased PP2A activity and activation of autophagic flux in HEK-293 cells and N2A cells and in patient-derived iNeurons, as indicated by changes in autophagosome and autophagy receptor markers; this contributed to clearance of insoluble tau. Furthermore, treatment of PS19 transgenic mice for 1 month with KYP-2047 reduced tau burden in the brain and cerebrospinal fluid and slowed cognitive decline according to several behavioral tests. In addition, a reduction in an oxidative stress marker was seen in mouse brains after KYP-2047 treatment. This study suggests that inhibition of prolyl oligopeptidase could help to ameliorate tau-dependent neurodegeneration.
18F-FDG-Based Radiomics and Machine Learning
Authors: Thomas Godefroy, Gauthier Frécon, Antoine Asquier-Khati, Diana Mateus, Raphaël Lecomte, Mira Rizkallah, Nicolas Piriou, Bastien Jamet, Thierry Le Tourneau, Amandine Pallardy, David Boutoille, Thomas Eugène, Thomas Carlier
Journal: JACC. Cardiovascular imaging (2023)
Association of Right Ventricular Myocardial Blood Flow With Pulmonary Pressures and Outcome in Cardiac Amyloidosis
Authors: Hendrik J. Harms, Tor Clemmensen, Sara Rosengren, Lars Tolbod, Björn Pilebro, Gerhard Wikström, Sven-Olof Granstam, Tanja Kero, Marcelo Di Carli, Steen Hvitfeldt Poulsen, Jens Sorensen
Journal: JACC. Cardiovascular imaging (2023)
The Use and Efficacy of FFR-CT
Authors: Tarun K. Mittal, Sandeep S. Hothi, Vinod Venugopal, John Taleyratne, David O’Brien, Kazi Adnan, Joban Sehmi, Georgios Daskalopoulos, Aparna Deshpande, Sara Elfawal, Vinoda Sharma, Rajai A. Shahin, Mengshi Yuan, Dominik Schlosshan, Andrew Walker, Saif-El-Dean Abdel Rahman, Imran Sunderji, Sidhesh Wagh, Jocelyn Chow, Mohammed Masood, Sumeet Sharma, Sharad Agrawal, Chary Duraikannu, Elisa McAlindon, Saeed Mirsadraee, Edward D. Nicol, Andrew D. Kelion
Journal: JACC. Cardiovascular imaging (2023)
Association of Inflammation and Lipoprotein(a) With Aortic Valve Calcification
Authors: Natalie Marrero, Alexander C. Razavi, Ellen Boakye, Khalil Anchouche, Zeina Dardari, Omar Dzaye, Kunal Jha, Matthew J. Budoff, Michael Y. Tsai, Jerome I. Rotter, Roger S. Blumenthal, George Thanassoulis, Wendy S. Post, Michael J. Blaha, Seamus P. Whelton
Journal: JACC. Cardiovascular imaging (2023)
Coronary Artery Stenosis Evaluation by Angiography-Derived FFR
Authors: Jelmer Westra, Laust Dupont Rasmussen, Ashkan Eftekhari, Simon Winther, Salma Raghad Karim, Jane Kirk Johansen, Osama Hammid, Hanne Maare Søndergaard, June Anita Ejlersen, Lars C. Gormsen, Lone Juul Hune Mogensen, Morten Bøttcher, Niels Ramsing Holm, Evald Høj Christiansen
Journal: JACC. Cardiovascular imaging (2023)
Impact of Persistent Microvascular Obstruction Late After STEMI on Adverse LV Remodeling
Authors: Vicente Bodi, Jose Gavara, Maria P. Lopez-Lereu, Jose V. Monmeneu, Elena de Dios, Nerea Perez-Sole, Clara Bonanad, Victor Marcos-Garces, Joaquim Canoves, Gema Minana, Julio Nunez, David Moratal, Francisco J. Chorro, Jose F. Rodríguez-Palomares, Andrea Freixa, Roger Borrás, Jose T. Ortiz-Pérez, Cesar Rios-Navarro
Journal: JACC. Cardiovascular imaging (2023)
Pulmonary Artery Strain Predicts Prognosis in Pulmonary Arterial Hypertension
Authors: Liang Zhong, Shuang Leng, Samer Alabed, Ping Chai, Lynette Teo, Wen Ruan, Ting-Ting Low, James M. Wild, John C. Allen, Soo Teik Lim, Ju Le Tan, James Wei-Luen Yip, Andrew J. Swift, David G. Kiely, Ru-San Tan
Journal: JACC. Cardiovascular imaging (2023)
CT Coronary Angiography and Dynamic CT Myocardial Perfusion for Detection of Cardiac Allograft Vasculopathy
Authors: Yura Ahn, Hyun Jung Koo, Junho Hyun, Sang Eun Lee, Sung Ho Jung, Duk-Woo Park, Jung-Min Ahn, Do-Yoon Kang, Seung-Jung Park, Hee Sang Hwang, Joon-Won Kang, Dong Hyun Yang, Jae-Joong Kim
Journal: JACC. Cardiovascular imaging (2023)
Characterization of the endotheliopathy, innate-immune activation and hemostatic imbalance underlying CAR-T cell toxicities: laboratory tools for an early and differential diagnosis
Authors: Ana Belen Moreno-Castaño, Sara Fernández, Helena Ventosa, Marta Palomo, Julia Martinez-Sanchez, Alex Ramos, Valentín Ortiz-Maldonado, Julio Delgado, Carlos Fernández de Larrea, Alvaro Urbano-Ispizua, Olaf Penack, J M Nicolás, Adrian Téllez, Gines Escolar, Enric Carreras, Francesc Fernández-Avilés, Pedro Castro, Maribel Diaz-Ricart
Journal: Journal for ImmunoTherapy of Cancer (2023)

Chimeric antigen receptor (CAR)-T cell-based immunotherapy constitutes a revolutionary advance for treatment of relapsed/refractory hematological malignancies. Nevertheless, cytokine release and immune effector cell-associated neurotoxicity syndromes are life-threatening toxicities in which the endothelium could be a pathophysiological substrate. Furthermore, differential diagnosis from sepsis, highly incident in these patients, is challenging. Suitable laboratory tools could be determinant for their appropriate management.Sixty-two patients treated with CAR-T cell immunotherapy for hematological malignancies (n=46 with CD19-positive diseases, n=16 with multiple myeloma) were included. Plasma samples were obtained: before CAR-T cell infusion (baseline); after 24-48 hours; at suspicion of any toxicity onset and 24-48 hours after immunomodulatory treatment. Biomarkers of endothelial dysfunction (soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble TNF receptor 1 (sTNFRI), thrombomodulin (TM), soluble suppression of tumorigenesis-2 factor (ST2), angiopoietin-2 (Ang-2)), innate immunity activation (neutrophil extracellular traps (NETs), soluble C5b-9 (sC5b-9)) and hemostasis/fibrinolysis (von Willebrand Factor antigen (VWF:Ag), ADAMTS-13 (A13), α2-antiplasmin (α2-AP), plasminogen activator inhibitor-1 antigen (PAI-1 Ag)) were measured and compared with those in cohorts of patients with sepsis and healthy donors.Patients who developed CAR-T cell toxicities presented increased levels of sVCAM-1, sTNFRI and ST2 at the clinical onset versus postinfusion values. Twenty-four hours after infusion, ST2 levels were good predictors of any CAR-T cell toxicity, and combination of ST2, Ang-2 and NETs differentiated patients requiring intensive care unit admission from those with milder clinical presentations. Association of Ang-2, NETs, sC5b-9, VWF:Ag and PAI-1 Ag showed excellent discrimination between severe CAR-T cell toxicities and sepsis.This study provides relevant contributions to the current knowledge of the CAR-T cell toxicities pathophysiology. Markers of endotheliopathy, innate immunity activation and hemostatic imbalance appear as potential laboratory tools for their prediction, severity and differential diagnosis.
Specific recognition of an<i>FGFR2</i>fusion by tumor infiltrating lymphocytes from a patient with metastatic cholangiocarcinoma
Authors: Bradley Sinclair White, Sivasish Sindiri, Victoria Hill, Billel Gasmi, Shirley Nah, Jared J Gartner, Todd D Prickett, Yong Li, Devikala Gurusamy, Paul Robbins, Steven A Rosenberg, Vid Leko
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions. In this context, fusions that involve fibroblast growth factor receptor 2 ( FGFR2 ) and function as oncogenes in a subset of patients with intrahepatic CC (ICC) represent particularly attractive targets for adoptive cell therapy. However, no study to date has explored whether FGFR2 fusions can be recognized by patients’ T cells. Method To address whether FGFR2 fusions can be recognized by patients’ T cells, we tested TILs from four patients with FGFR2 fusion-positive ICC for recognition of peptides and minigenes that represented the breakpoint regions of these fusions, which were unique to each of the four patients. Results We found that CD4 + TILs from one patient specifically recognized the breakpoint region of a unique FGFR2-TDRD1 (tudor domain-containing 1) fusion, and we isolated a T-cell receptor responsible for its recognition. Conclusions This finding suggests that FGFR2 fusion-reactive TILs can be isolated from some patients with metastatic ICC, and thus provides a rationale for future exploration of T cell-based therapy targeting FGFR2 fusions in patients with cancer. Furthermore, it augments the rationale for extending such efforts to other types of solid tumors hallmarked by oncogenic gene fusions.
Evaluating the impact of a virtual outpatient care programme in preventing hospitalizations, emergency department visits and mortality for patients with COVID-19: a matched cohort study
Authors: Mei-Ni Belzile, Philip Lam, Adrienne K. Chan, Nisha Andany, Andrew E. Simor, Jose Estrada-Codecido, Amal Ga'al, Abby Kapsack, Abdalla Mahmud, Daniel Fridman, Samantha M. Lee, Aimee Santoro, Nancy Vandenbergh, Nick Daneman
Journal: Clinical Microbiology and Infection (2023)
Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles
Authors: Mukeng Hong, Zhuang Li, Haihua Liu, Songyuan Zheng, Fangling Zhang, Junqing Zhu, Hao Shi, Haixing Ye, Zhantu Chou, Lei Gao, Jianxin Diao, Yang Zhang, Dongxin Zhang, Shixian Chen, Hongwei Zhou, Juan Li
Journal: Cell Host & Microbe (2023)
Correction:<i>The effect of achieving serological remission on subsequent risk of relapse, end-stage renal disease and mortality in ANCA-associated vasculitis: a target trial emulation study</i>
Journal: Annals of the Rheumatic Diseases (2023)

CorrectionCorrection: The effect of achieving serological remission on subsequent risk of relapse, end-stage renal disease and mortality in ANCA-associated vasculitis: a target trial emulation study
Cover Image, Volume 43, Issue 4
Authors: Hiroyuki Suzuki, Hideki Iwamoto, Takahiro Seki, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Yasuko Imamura, Takashi Niizeki, Masahito Nakano, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Miwa Sakai, Kazutoyo Morita, Masamichi Nakayama, Tomoharu Yoshizumi, Ryoko Kuromatsu, Hirohisa Yano, Yihai Cao, Hironori Koga, Takuji Torimura
Journal: Cancer Communications (2023)

The cover image is based on the Original Article Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors by Hiroyuki Suzuki et al., https://doi.org/10.1002/cac2.12411
Correction: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
Authors: Cheng-Cao Sun, Wei Zhu, Shu-Jun Li, Wei Hu, Jian Zhang, Yue Zhuo, Han Zhang, Juan Wang, Yu Zhang, Shao-Xin Huang, Qi-Qiang He, De-Jia Li
Journal: Genome Medicine (2023)
IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling
Authors: Holly Bachus, Erin McLaughlin, Crystal Lewis, Amber M. Papillion, Etty N. Benveniste, Dave Durell Hill, Alexander F. Rosenberg, André Ballesteros-Tato, Beatriz León
Journal: Cellular and Molecular Immunology (2023)

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
Posterior Polymorphous Corneal Dystrophy: Clinical-Pathologic Correlation
Authors: Jordan Philip Safran, Kristin M. Hammersmith, Tatyana Milman
Journal: Ophthalmology (2023)

A 9-year-old girl presented with bilateral steep corneal curvatures (A) and crater-like vacuoles in posterior cornea (B, arrow), compatible with posterior polymorphous corneal dystrophy. Penetrating keratoplasty, performed for progressive corneal stromal opacification and calcific band keratopathy (B, asterisk) demonstrated epithelial-like multilayered cells on the posterior corneal surface (C, arrowheads) and, in posterior stroma, forming vesicles (thick arrow), associated with multilamination and discontinuity in Descemet's membrane (thin arrows) (C; hematoxylin-eosin; 1000×). These cells were positive for high molecular weight cytokeratin (D; 1000×), compatible with epithelial-like transdifferentiation of corneal endothelium. (Magnified version of Figure A-D is available online at www.aaojournal.org).
Inferences about interdependence shape cooperation
Authors: Daniel Balliet, Björn Lindström
Journal: Trends in Cognitive Sciences (2023)

During social interactions in daily life, people possess imperfect knowledge of their interdependence (i.e., how behaviors affect each person's outcomes), and what people infer about their interdependence can shape their behaviors. We review theory and research that suggests people can infer their interdependence with others along several dimensions, including mutual dependence, power, and corresponding-versus-conflicting interests. We discuss how perceptions of interdependence affect how people cooperate and punish others' defection in everyday life. We propose that people understand their interdependence with others through knowledge of the action space, cues during social interactions (e.g., partner behaviors), and priors based on experience. Finally, we describe how learning interdependence could occur through domain-specific and domain-general mechanisms.